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Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity

Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways. Sporulation factor IV B protease (SpoIVB) and C-terminal processing proteases B (CtpB) play central roles in cellular differentiation via regulated intramembrane proteo...

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Autores principales: Xie, Xie, Guo, Nannan, Xue, Guangpu, Xie, Daoqing, Yuan, Cai, Harrison, Joshua, Li, Jinyu, Jiang, Longguang, Huang, Mingdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581720/
https://www.ncbi.nlm.nih.gov/pubmed/31244791
http://dx.doi.org/10.3389/fmicb.2019.01232
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author Xie, Xie
Guo, Nannan
Xue, Guangpu
Xie, Daoqing
Yuan, Cai
Harrison, Joshua
Li, Jinyu
Jiang, Longguang
Huang, Mingdong
author_facet Xie, Xie
Guo, Nannan
Xue, Guangpu
Xie, Daoqing
Yuan, Cai
Harrison, Joshua
Li, Jinyu
Jiang, Longguang
Huang, Mingdong
author_sort Xie, Xie
collection PubMed
description Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways. Sporulation factor IV B protease (SpoIVB) and C-terminal processing proteases B (CtpB) play central roles in cellular differentiation via regulated intramembrane proteolysis (RIP) process which activates pro-σ(K) processing at the σ(K) checkpoint during spore formation. SpoIVB joins CtpB in belonging to the widespread family of PDZ-proteases, but much remains unclear about the molecular mechanisms and structure of SpoIVB. In this study, we expressed inactive SpoIVB (SpoIVB(S378A)) fused with maltose binding protein (MBP)-tag and obtained the solution structure of SpoIVB(S378A) from its small angle X-ray scattering (SAXS) data. The fusion protein is more soluble, stable, and yields higher expression compared to SpoIVB without the tag. MBP-tag not only facilitates modeling of the structure in the SAXS envelope but also evaluates reliability of the model. The solution structure of SpoIVB(S378A) fits closely with the experimental scattering data (χ(2)= 1.76). Comparing the conformations of PDZ-proteases indicates that SpoIVB adopts a PDZ-protease pattern similar to the high temperature requirement A proteases (HtrAs) rather than CtpB. We not only propose that SpoIVB uses a more direct and simple way to cleave the substrates than that of CtpB, but also that they work together as signal amplifiers to activate downstream proteins in the RIP pathway.
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spelling pubmed-65817202019-06-26 Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity Xie, Xie Guo, Nannan Xue, Guangpu Xie, Daoqing Yuan, Cai Harrison, Joshua Li, Jinyu Jiang, Longguang Huang, Mingdong Front Microbiol Microbiology Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways. Sporulation factor IV B protease (SpoIVB) and C-terminal processing proteases B (CtpB) play central roles in cellular differentiation via regulated intramembrane proteolysis (RIP) process which activates pro-σ(K) processing at the σ(K) checkpoint during spore formation. SpoIVB joins CtpB in belonging to the widespread family of PDZ-proteases, but much remains unclear about the molecular mechanisms and structure of SpoIVB. In this study, we expressed inactive SpoIVB (SpoIVB(S378A)) fused with maltose binding protein (MBP)-tag and obtained the solution structure of SpoIVB(S378A) from its small angle X-ray scattering (SAXS) data. The fusion protein is more soluble, stable, and yields higher expression compared to SpoIVB without the tag. MBP-tag not only facilitates modeling of the structure in the SAXS envelope but also evaluates reliability of the model. The solution structure of SpoIVB(S378A) fits closely with the experimental scattering data (χ(2)= 1.76). Comparing the conformations of PDZ-proteases indicates that SpoIVB adopts a PDZ-protease pattern similar to the high temperature requirement A proteases (HtrAs) rather than CtpB. We not only propose that SpoIVB uses a more direct and simple way to cleave the substrates than that of CtpB, but also that they work together as signal amplifiers to activate downstream proteins in the RIP pathway. Frontiers Media S.A. 2019-06-12 /pmc/articles/PMC6581720/ /pubmed/31244791 http://dx.doi.org/10.3389/fmicb.2019.01232 Text en Copyright © 2019 Xie, Guo, Xue, Xie, Yuan, Harrison, Li, Jiang and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Xie, Xie
Guo, Nannan
Xue, Guangpu
Xie, Daoqing
Yuan, Cai
Harrison, Joshua
Li, Jinyu
Jiang, Longguang
Huang, Mingdong
Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
title Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
title_full Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
title_fullStr Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
title_full_unstemmed Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
title_short Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
title_sort solution structure of spoivb reveals mechanism of pdz domain-regulated protease activity
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581720/
https://www.ncbi.nlm.nih.gov/pubmed/31244791
http://dx.doi.org/10.3389/fmicb.2019.01232
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